Tumor-expressed GPNMB orchestrates Siglec-9⁺ TAM polarization and EMT to promote metastasis in triple-negative breast cancer.

ABSTRACT: Metastasis remains the leading cause of cancer-related mortality, driven by complex interactions within the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) play a pivotal role in metastatic progression, yet their molecular diversity and upstream regulators remain poorly defined. Glycoprotein nonmetastatic melanoma protein B (GPNMB), overexpressed in subsets of tumors including triple-negative breast cancer (TNBC), is implicated in epithelial-mesenchymal transition (EMT) and cancer stemness. Recent single-cell RNA sequencing (scRNA-seq) identified GPNMB as a marker of immunosuppressive TAMs associated with poor prognosis, but its mechanistic role in TNBC has remained unclear. Coculturing monocytic cells with three-dimensional TNBC spheres induced GPNMB⁺ TAMs exp

SUBMITTER: Dang Cao TL 

PROVIDER: S-EPMC12435292 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature